The present invention relates to microneedle structures and, in particular, it concerns a microneedle production method and the microneedle structure produced thereby.
Much research has been directed towards the development of microneedles formed on chips or wafers by use of micro-machining techniques. This approach promises the possibility of producing numerous, very small needles which are sufficient to form small perforations in the dermal barrier, thereby overcoming the molecular size limitations of conventional transdermal patches, while being safe for use by unqualified personnel. Examples of such work may be found in PCT Publication No. WO 99/64580 to Georgia Tech Research Corp., as well as in the following scientific publications: “Micro machined needles for the transdermal delivery of drugs”, S. H. S. Henry et al. (MEMS 98, Heildelberg, Germany, January 1998); “Three dimensional hollow micro needle and microtube arrays”, D. V. McAllister et al. (Transducer 99, Sendai, Japan, June 1999); “An array of hollow micro-capillaries for the controlled injection of genetic materials into animal/plant cells”, K. Chun et al. (MEMS 99, Orlando, Fla., January 1999); and “Injection of DNA into plant and animal tissues with micromechanical piercing structures”, W. Trimmer et al. (IEEE workshop on MEMS, Amsterdam, January 1995). The more recent of these references, namely, the Georgia Tech application and the Chun et al. reference, disclose the use of hollow microneedles to provide a flow path for fluid flow through the skin barrier.
While hollow microneedles are potentially an effective structure for delivering fluids across the dermal barrier, the structures proposed to-date suffer from a number of drawbacks. Most notably, the proposed structures employ microneedles with flat hollow tips which tend to punch a round hole through the layers of skin. This punching action tends to cause damage to the skin. Additionally, the punched material tends to form a plug which at least partially obstructs the flow path through the microneedle. This is particularly problematic where withdrawal of fluids is required since the suction further exacerbates the plugging of the hollow tube within the microneedle. The flat ended form of the needles also presents a relatively large resistance to penetration of the skin, reducing the effectiveness of the structure.
A further group of proposed devices employ microneedles formed by in-plane production techniques. Examples of such devices are described in U.S. Pat. No. 5,591,139 to Lin et al., U.S. Pat. No. 5,801,057 to Smart et al., and U.S. Pat. No. 5,928,207 to Pisano et al. The use of in-plane production techniques opens up additional possibilities with regard to the microneedle tip configuration. This, however, is at the cost of very limited density of microneedles (either a single microneedle, or at most, a single row of needles), leading to corresponding severe fluid flow rate limitations. The very long proposed needle (about 3 mm) of Smart et al. suffers from an additional very high risk of needle breakage.
Co-pending U.S. patent application Ser. No. 09/589,369, which is unpublished at the date of filing this application and which does not constitute prior art, proposes an improved out-of-plane hollow microneedle structure having an aperture which is located behind a non-hollow piercing tip. The application describes a number of production techniques for such structures, including techniques based upon either dry etching or by combining wet etching techniques with asymmetric abrasion.
While the techniques described in the aforementioned co-pending application produce highly effective microneedle structures, various disadvantages are encountered while implementing such techniques in commercial production. Firstly, conventional deep reactive ion etching (DRIE) is generally sufficiently inaccurate to reduce the usable yield to unacceptably low proportions. Accuracy can be greatly improved by using cryogenic dry etching techniques. This option, however, greatly reduces the rate at which material can be etched away. As a result, these techniques are inefficient processing large areas of a wafer. Wet techniques, on the other hand, are efficient for simultaneous processing of large regions of a wafer and offer high accuracy. Wet techniques are not, however, suited for directly achieving the asymmetrical forms required for implementation of the microneedles.
A further shortcoming of microneedle structures made by micromachining techniques is the brittleness of the resulting microneedles. Microneedles made from silicon or silicon dioxide are highly brittle. As a result, a significant proportion of the microneedles may fracture due to the stresses occurring during penetration, leaving fragments of the material within the tissue. Furthermore, oblique insertion by an unskilled person could lead to fracture of a very large proportion of the needles, resulting in malfunction of the device.
There is therefore a need for a method for producing hollow microneedles which would combine the advantages of dry and wet etching techniques to offer an effective and reliable production technique. It would also be highly advantageous to provide microneedle structures produced by such production methods.